Risultati per: Linee Guida per le cure post-parto

Circulation, Volume 150, Issue Suppl_1, Page A4141509-A4141509, November 12, 2024. Background:Dietary stearic acid (18:0), a saturated fatty acid (SFA) commonly present in Western diets, has an LDL-C lowering effect compared to shorter chain SFAs such as palmitic acid (16:0), and a similar effect compared to oleic acid (18:1). However, the underlying mechanisms remain unclear.Hypothesis:We tested the hypothesis that the hypocholesterolemic effect of dietary 18:0 and 18:1 relative to 16:0 is modulated by alterations in cholesterol and bile acid (BA) metabolism.Methods:This secondary analysis used archived plasma and fecal samples from a randomized crossover feeding study (N=20 mildly hypercholesteremic postmenopausal women, 64±7 years, BMI 26.4±3.4kg/m2). Participants consumed each of 3 isocaloric diets enriched in either 18:0, 16:0 or 18:1 for five weeks with a 2-week washout. Primary (P) and secondary (S) BAs, and their conjugates were measured in fecal, fasting and non-fasting (NF) plasma samples using the Biocrates MxP Quant 500 kit and Quadrupole Time-of-Flight mass spectrometry. Fasting and NF plasma cholesterol synthesis (lathosterol) and absorption (-sitosterol) markerswere quantified using gas chromatography. Mixed-effect and generalized linear mixed models were used to test the difference in outcome measures among diets, with Tukey-Kramer post hoc comparison. Spearman correlation coefficients with FDR adjustment was calculated between BA, cholesterol synthesis/absorption markers, and CVD risk factors.Results:Compared to the 16:0 diet, consumption of the 18:0 diet resulted in significantly lower fasting and NF plasma lathosterol (-22%); higher -sitosterol (19%); higher fecal PBAs (31%) and lower fecal SBAs (-17%) concentrations. Plasma PBAs were significantly lower in the fasted state (-34%), but higher in the NF state (21%; 18:0 vs. 16:0). Interestingly, conjugated PBA and SBA concentrations in the NF state were significantly higher after participants consumed the 18:0 compared to the 18:1 diet (all p

Circulation, Volume 150, Issue Suppl_1, Page A4139454-A4139454, November 12, 2024. Introduction:Atrial Fibrillation (AF) incidence increased by 30% over the past 20 years with 1 of 7 strokes attributed to AF. While catheter ablation (CA) is valuable at decreasing AF burden, its long-term effect on stroke risk is unknown. 4D flow MRI studies of AF patients have found reduced peak velocities and increased blood stasis in the left atrium (LA) and LA appendage (LAA), indicating AF-associated atrial flow impairment and increased thromboembolism risk.Aim:To explore, using 4D flow MRI, pre vs post-CA LA and LAA hemodynamics and volumes in patients with and without AF recurrence.Methods:We enrolled 60 AF patients who had baseline (pre-CA) and follow-up (post-CA) 4D-flow MRI scans. Success was defined as no recurrent AF > 30 sec on intermittent monitoring after a 3-month blanking period. 4D flow data analysis included pre-processing and LA/LAA manual 3D segmentation. The segmentations were used to calculate LA and LAA volumes as well as peak velocity and blood stasis (Figure 1).Results:Of the 60 patients (61.1 ± 12.3 years, 73% male), forty-five maintained SR while 15 had AF recurrence post-CA. One LAA was excluded from the analysis due to the presence of an artifact.Mean LA stasis significantly decreased for both groups post-CA (success: 46 ± 17% to 41 ± 11% and failure: 40 ± 13% to 37 ± 12%, p

Circulation, Volume 150, Issue Suppl_1, Page A4136204-A4136204, November 12, 2024. Introduction:Cellular senescence often involves a p16-pathway, and p16 overexpression is a hallmark of senescent cells. The role of cellular senescence in myocardial infarction (MI) and any mediating mechanisms remain unclear.Aims:To investigate the effect of p16+cell clearance on survival post MI and elucidate underlying mechanisms.Methods:We utilized INK-ATTAC transgenic mice, in which p16+cells undergo targeted apoptosis upon exposure to AP20187 (AP). Sham and MI mice were treated with AP or vehicle (V) twice-weekly for one month, starting 3-4 hours post-MI. Survival rate improvement post MI in the AP group (Fig A, P

Circulation, Volume 150, Issue Suppl_1, Page A4139933-A4139933, November 12, 2024. Introduction:Calcific aortic valve stenosis is the more frequent valvular disease, affecting more than 10% of patients >75 years old. Surgical or transcatheter aortic valve replacement is the only treatment available. There is an increase use of bioprosthetic valves, even if they present a limited durability with the progressive development of structural bioprosthetic deterioration (SVD). Recent clinical studies highlighted an association between circulating lipid factors, such as proprotein convertase subtilisin/kexin type 9 (PCSK9), Lipoprotein (a) and LDL-cholesterol, and SVD. However, the underlying mechanisms remain unknown.Objective:We aim at deciphering the role of hypercholesterolemia and/or PCSK9 on the early processes leading to SVD.Methods:Subcutaneous implantation of bioprosthetic tissue was performed on 10-week old wild type (WT), PCSK9 knock-out (KO) and PCSK9 overexpressing C57BL/6J mice for 28 days. A qualitative anatomopathological score evaluating cell density, infiltration, and tissue degradation was developed. Infiltrated immune cells were characterized by IHC, with a focus on anti- (CD163+) and pro-inflammatory (F4/80+) macrophages, lymphocytes (CD3+) and polynuclear eosinophils (CCR3+).Results:An important infiltration of mononuclear cells into the explanted punches was observed among the 3 groups (n=10 mice/group). Cell recruitment was more pronounced in mice overexpressing PCSK9 compared to WT and KO. The anatomopathological score of PCSK9 overexpressing mice was significantly higher as compared to WT and KO (7.0 [4.1-8.4] vs 4.0 [3.0-4.5] and 2.8 [2.0-3.9], respectively; p=0.008). The infiltrate was mainly composed of macrophages (CD163+ F4/80+) and polynuclear eosinophils, even if few lymphocytes were observed. Polynuclear eosinophils were more abundant in mice overexpressing PCSK9 compared to WT and KO (p=0.01 and p=0.002).Conclusion:Hypercholesterolemia and/or high PCSK9 level promote the cellular response against the bioprosthetic tissue. It potentiates the infiltration of polynuclear eosinophils and macrophages, pointing out for an exacerbated inflammatory response, post implantation. Deeper cellular/molecular analyses are ongoing to provide mechanistic clues to better understand the link between hypercholesterolemia/PCSK9 and the early inflammatory processes leading to SVD.

Circulation, Volume 150, Issue Suppl_1, Page A4141358-A4141358, November 12, 2024. Background:Tirzepatide is a once weekly GIP and GLP-1 receptor agonist approved for the treatment of type 2 diabetes (T2D) and obesity. This post hoc analysis evaluated the contribution of body weight reduction-associated and -unassociated effects on the lipid profile of tirzepatide-treated participants living with obesity, without and with T2D, from the SURMOUNT-1 and SURMOUNT-2 clinical trials, respectively.Methods:Participants treated with tirzepatide (pooled doses of 5, 10, 15 mg in SURMOUNT-1 [N=1765] and 10 and 15 mg in SURMOUNT-2 [N=587]) were included in this analysis. The estimated treatment effects and the body weight reduction-associated and -unassociated attribution on changes from baseline in lipid profile (total cholesterol, HDL-C, LDL-C, non-HDL-C, VLDL-C, and triglycerides) at 24 and 72 weeks were assessed via the SAS CAUSALMED procedure.Results:In SURMOUNT-1, after 24 weeks of tirzepatide treatment in participants without T2D, 69-85% of the changes in total cholesterol, HDL-C, LDL-C, and non-HDL-C, and 41-43% of the changes in VLDL-C and triglycerides occurred unassociated with body weight reduction (Table). At 72 weeks, most of the effect on the lipid profile was associated with body weight reduction. In SURMOUNT-2, after 24 weeks of tirzepatide treatment in participants with T2D, most of the changes in the lipid profile occurred unassociated with body weight reduction. At 72 weeks, changes observed in the lipid profile were predominantly associated with body weight reduction, although 43-50% of those changes also occurred unassociated with body weight reduction, except for LDL-C which was almost completely (92%) associated with body weight reduction.Conclusions:In this post hoc analysis from SURMOUNT-1 and SURMOUNT-2, changes in lipid profile were mostly unassociated with body weight reduction after 24 weeks of tirzepatide treatment and associated with of body weight reduction at 72 weeks. Body weight reduction-unassociated mechanisms responsible for the initial changes in lipid profile in participants with obesity treated with tirzepatide warrants further research studies.

Circulation, Volume 150, Issue Suppl_1, Page A4146276-A4146276, November 12, 2024. Background:The first-ever genetically modified porcine-to-human cardiac xenotransplantation was performed in January 2022 at the University of Maryland, with the recipient surviving 60 days.Aim:Characterize trends in conduction delay observed over the 60-day post-operative course of the first-ever porcine-to-human cardiac xenotransplant recipient.Methods:Daily 12-lead ECGs were evaluated for presence and type of conduction delay. Over the post-operative period, 93 ECGs were obtained. ECGs that could not be assessed for conduction delay due to presence of significant artifact (2 ECGs) or paced rhythm (12 ECGs) were excluded from evaluation.Results:During the 60-day postoperative period, the xenotransplant exhibited alternating conduction block including nonspecific intraventricular conduction delay (NSIVCD), right bundle branch block (RBBB), incomplete RBBB, and left anterior fascicular block (LAFB). Nonspecific intraventricular conduction delay (NSIVCD) was observed on 6 days in total, occurring primarily within the first 9 post-operative days. After day 9, the conduction block alternated between bifascicular block with RBBB+LAFB, incomplete RBBB+LAFB, RBBB, and incomplete RBBB. The predominant pattern of conduction delay was bifascicular block with RBBB+LAFB, occurring over 32 days in this period. Presence of incomplete RBBB+LAFB was noted on 17 days in total. Isolated RBBB occurred on 2 days, and incomplete RBBB on 4 days. There was no evidence of high-grade atrioventricular block observed in this period.Conclusion:Ventricular conduction in the post-operative period of the first porcine-to-human xenotransplant was characterized by an alternating conduction block with NSIVCD in the early postoperative period (through day 9), followed by predominantly bifascicular block with RBBB and LAFB or incomplete RBBB and LAFB. Atrioventricular conduction remained largely intact without evidence of high-grade AV block nor dependence on back-up pacing during the majority of our patient’s post-operative course.

Circulation, Volume 150, Issue Suppl_1, Page A4144690-A4144690, November 12, 2024. Background:High-density lipoproteins (HDLs) have various potentially beneficial circulatory effects. Apolipoprotein A-1, one of the HDL mimetics, has been shown in several studies to slow the progression of atherosclerosis after an acute coronary syndrome (ACS) event.Aim:To evaluate the comparative efficacy of Apo A1 on Total Atheroma Volume (TAV), Percent Atheroma Volume (PAV), and changes in these parameters.Methods:We systematically searched articles in PubMed, Web of Science, Cochrane Central Register of Controlled Trials (CENTRAL), and Embase published up to June 2024. Eligible randomized controlled trials (RCTs) enrolled adults who received Apo A1 infusion, compared to placebo, within 2 weeks of an ACS event (defined as unstable angina, non-ST or ST-segment elevation myocardial infarction) or with at least one narrowing of ≥20% on coronary angiography at baseline. Apo A1 infusion preparations evaluated include ETC-216, CER-001, CSL-111, and MDCO-216. Network meta-analysis was performed.Results:A total of 5 RCTs were included in our analysis. Outcomes evaluated include PAV, TAV (measured by intravascular ultrasonography catheter), and changes in these values from baseline to follow-up. For changes in PAV, only ETC-216 45 mg was statistically significant (MD: -12.74, [-20.70; -4.78]). All other regimens were statistically insignificant: ETC-216 15 mg, ETC-216 15 and 45 mg combined, CER-001 3 mg, CER-001 6 mg, CER-001 12 mg, MDCO-216 20 mg, and CSL-111 40 or 80 mg. In addition, changes in TAV showed no significant treatment effects. PAV was lowest at follow-up in the CER-001 3 mg (MD: -1.68, [-4.73; 1.38]) and MDCO-216 20 mg (MD: 1.00, [-3.64; 5.64]) groups; all other ETC-216 and CER-001 regimens were insignificant. For TAV, only MDCO-216 20 mg (MD: -10.00, [-39.58; 19.58]) and CER-001 3 mg (MD: -2.47, [-19.84; 14.90]) showed insignificant treatment effects, while all ETC-216 regimens had no beneficial effect.Conclusion:Our analysis concludes that ETC-216, 45 mg showed a significant reduction in PAV. Other regimens were insignificant in their effect on atheroma reduction. This analysis highlights the need for further clinical trials to explore this regimen for enhancing responses in ACS patients.

Circulation, Volume 150, Issue Suppl_1, Page A4143118-A4143118, November 12, 2024. Introduction:Left atrial (LA) fibrosis identified by delayed enhancement MRI has been linked to poor outcomes post-AF ablation. We aim to assess the relationship between LA fibrosis and post-ablation AF burden in a persistent AF population.Methods:This is a subanalysis from the DECAAF II trial which included persistent AF undergoing catheter ablation. Delayed enhancement MRI was performed up to 30 days pre-ablation. Fibrosis was quantified at a core lab and categorized into 4 stages: 1 (

Circulation, Volume 150, Issue Suppl_1, Page A4140906-A4140906, November 12, 2024. Background and Aims:Functional complete revascularization (FCR) subsequent to percutaneous coronary intervention (PCI), as assessed by the residual functional SYNTAX score (rFSS), has been correlated with enhanced prognostic outcomes. This study sought to comprehensively apprehend the adverse cardiovascular prognosis within diabetic cohorts, determining what extent the association of diabetes with clinical outcomes is explained by functional revascularization.Methods:A total of 1,555 patients with available post-PCI quantitative flow ratio (QFR) were included, whose data were collected from PANDA III trial (Figure 1). FCR was defined as rFSS = 0, while anatomic complete revascularization (ACR) was defined as residual SYNTAX score (rSS) = 0. Firstly, we determined the ACR and FCR among DM and non-DM cohorts. Second, multiple cox regression was used to screen for potential mediating variables. Finally, we used structural equation modeling to analysis whether FCR explained the relationship between DM and the risk of 2-year rates of major adverse cardiac events (MACE).Results:Patients with DM had a significant lower percentage of FCR (71.9% vs 80.2%, P

Circulation, Volume 150, Issue Suppl_1, Page A4141782-A4141782, November 12, 2024. CD8+T-cells are adverse regulators post myocardial infarction (MI), leading to increased mortality and impaired cardiac function. We hypothesize that CD8+T-cells impair cardiac function by altering scar composition.MI was induced by ligating the left anterior descending coronary artery in C57BL6/J (WT; 3-7 months of age, n≥2/sex) and CD8atm1makmice (CD8-/-; 3-7 months of age, n≥2/sex/treatment). CD8-/-mice were injected with either vehicle or naïve splenic CD8+T-cells (2x106cells/injection) via tail vein, 4 hours post-MI. Infarct tissue was collected post-MI Day 7 and underwent biomechanical, histological, and biochemical analyses. Effects of granzyme (Gzm) A, B, and K on collagen cleavage were tested using a fluorogenic collagen cleavage assay to examine possible mechanisms of scar alteration.Mice lacking CD8+T-cells had improved ejection fraction and decreased dilation (p

Circulation, Volume 150, Issue Suppl_1, Page A4144944-A4144944, November 12, 2024. Background:The American Heart Association’s (AHA) Life’s Essential 8 (LE8) concept serves as a quantitative framework for assessing cardiovascular health (CVH). Post-operative coronary artery bypass graft (CABG) and percutaneous coronary intervention (PCI) patients are at high-risk for subsequent cardiovascular events (CVE). However, LE8 scores for post-procedural CABG or PCI patients remain unknown.Methods:Isolated post-operative CABG (n=208) or PCI (n=739) non-institutionalized patients from the National Institutes of Health’s (NIH) All of Us (AoU) Research Program (2017-2022) were included. LE8 scores (range 0-100, higher = better CVH; excluding diet metric) were calculated using methods recommended by the AHA. Physical activity and sleep metrics were derived from patients’ Fitbit data, while all other metrics were sourced from electronic health records (EHR).Results:Overall LE8 scores for post-operative CABG (57.9 [95% CI: 56.6-59.2]) and PCI patients (55.3 [54.4-56.1]) were significantly lower than that of the general population (65.9 [65.1-66.7] (p

Circulation, Volume 150, Issue Suppl_1, Page A4141547-A4141547, November 12, 2024. Introduction:Branched chain amino acids (BCAAs) are essential amino acids that are elevated in the failing heart and that have been linked with cardiovascular disease risk. Yet, it remains unclear how BCAAs influence the heart after injury. In this study, we examined in mice whether dietary alterations of BCAA levels influences cardiac structure and function after myocardial infarction (MI).Methods and Results:To assess whether altering dietary BCAA levels would impact circulating BCAA concentrations, mice were fed a low (1/3×), normal (1×), or high (2×) BCAA diet over a 7-day period. The low and high BCAA diets were matched for macronutrient content, nitrogen content, and caloric density. We found that mice fed the low BCAA diet had >2-fold lower circulating BCAA concentrations when compared with normal and high BCAA diet feeding strategies (n=8/group; p

Circulation, Volume 150, Issue Suppl_1, Page A4140074-A4140074, November 12, 2024. Background:Long QT syndrome (LQTS) is a potentially lethal cardiac channelopathy. Among women with LQT2, the post-partum period has been considered high risk for cardiac events. However, whether this risk persists after establishing their diagnosis and implementing their LQT2-directed treatment program remains to be determined.Objective:To describe the management and outcomes of LQT2 women during the 9 months post-partum period.Methods:A retrospective analysis of 1869 patients with LQTS treated and evaluated at a tertiary center specializing in Genetic Heart Disease from January 2000 to November 2023 was performed to identify women with diagnosed and treated LQT2 who had a pregnancy during follow-up. Data were abstracted for patient demographics, clinical characteristics, symptomatic status, and treatment plans before and after pregnancy.Results:Overall, 30 pregnancies occurred in 22 women with LQT2. Their average QTc was 489 ± 34 ms with 7 patients (32%) having a resting QTc > 500 ms. Prior to their first post-partum period, 5/22 (23%) were symptomatic with 2 (9%) experiencing a LQT2-triggered sudden cardiac arrest (SCA). Before their post-partum period, their LQT2-directed therapy comprised preventative measures only in 7 (23%), drug therapy in 16 (53%), combination therapy in 7 (23%), and 10 women (43%) had an implantable cardioverter defibrillator (ICD). Pre-emptive treatment intensification was done for 24/30 post-partum periods. Only a single VF-terminating ICD therapy occurred in 1 (3%) of the 30 post-partum periods involving a 21-year-old with p.Lys610Asn-KCNH2 variant, QTc = 490 ms, and a pre-diagnosis presentation of seizures.Conclusion:Although the post-partum period is regarded as a ‘high risk’ window of time for women with LQT2, the risk of a LQT2-triggered cardiac event after diagnosis and implementation of contemporary therapies is very low. This designation of “high risk” among correctly diagnosed and treated women is misleading and generates inappropriate and unnecessary anxiety.

Circulation, Volume 150, Issue Suppl_1, Page A4125667-A4125667, November 12, 2024. Background:Renal denervation (RDN) has been shown in randomized trials to improve blood pressure compared with a sham procedure. Currently, there are two FDA-approved RDN devices in the United States (US). While nearly half of the US population has hypertension (HTN), the number of patients who may benefit from RDN therapy remains uncertain. In this study, we used a nationally representative dataset to approximate the proportion of patients with HTN who may be eligible for consideration of RDN based on selective criteria.Methods:All adult patients with HTN who participated in the National Health and Nutrition Examination Survey (NHANES) between the years 2009-2020 were identified. We characterized the proportion of these participants that met eligibility criteria based on 1) the FDA indication, 2) the SCAI 2023 RDN position statement, and 3) enrollment criteria from the RDN on-medication randomized trials. National estimates were obtained utilizing survey weighting from the NHANES multistage probability survey design.Results:In total, we identified 16,677 patients with HTN in the US, representing a weighted total of 113,786,149 patients (Table). Using the FDA indication, 31.6% (95% CI, 30.7%-32.6%) of patients meet eligibility criteria for RDN, corresponding to 35,988,870 US adults. By the SCAI 2023 position statement selection criteria, 21.5% (95% CI, 20.7%-22.3%) of patients are eligible for consideration of RDN. Based on enrollment criteria from the RDN on-medication randomized trials, 2.05% (95% CI, 1.81%-2.33%) of US adults meet eligibility for consideration of RDN (Figure).Conclusions:Our findings indicate that nearly one third of US adults with HTN are eligible for consideration of RDN based on the FDA indication; however, a smaller proportion of patients would be eligible based upon society recommendations and randomized trial inclusion criteria. Future studies are needed to further inform which patients will best benefit from this intervention.

Circulation, Volume 150, Issue Suppl_1, Page A4140452-A4140452, November 12, 2024. Background:The recent REDUCE-AMI trial showed no benefit to beta-blockers (BB) for patients post-myocardial infarction (MI) with preserved ejection fraction (EF≥50%). Target doses were metoprolol 100 mg and bisoprolol 5 mg daily (50% of the target doses used in the initial randomized clinical trials [RCTs] of BB post-MI).Research question:Do lower BB doses improve survival in post-MI patients with EF≥50%?Aims:To compare the effect of BB dose on all-cause mortality post-MI in patients with EF≥50%.Methods:This is a sub-study from the OBTAIN prospective multi-center registry. Of 7057 patients enrolled with acute MI, 3402 with EF≥50% were discharged alive (age:62.5±13.4 years, 67% male, 28% diabetics, length of stay 6.1±6.0 days). Discharge BB dose was indexed to the target daily BB dose used in RCTs, reported as %. Dosage groups were >0-12.5%, >12.5-25%, >25-50%, and >50% of the target dose. Follow-up vital status was obtained by chart review, Social Security Death Index, or direct contact up to 3 years post-MI. Kaplan-Meier (KM) method was used to calculate three-year survival. Cox proportional hazard regression model was used to identify significant predictors and conduct univariate and multivariate analysis.Results:The KM 3 year survival estimates were 89.0% and 84.3% for patients on and off BB, respectively (unadjusted hazard ratio (HR)=0.66, p=0.012; adjusted HR=0.52, p=0.18). The KM 3 year survival estimates(figure) were 89.8%, 91.0%, 87.9%, and 83.1% for patients on >0-12.5%, >12.5-25%, >25- 50%, and >50% of the BB target dose (unadjusted HR of 0.58, p=0.007; 0.58, p=0.003; 0.70; p=0.066; and 0.98, p=0.93), respectively, compared to no BB. After multivariate analysis, BB target dose showed similar trend, but not statistically significant (adjusted HR=0.65, p=0.46; 0.42, p=0.13; 0.53, p=0.31; 1.01, p=0.92).Conclusion:In OBTAIN, patients treated with low dose BB (≤25% of the target dose) had improved survival post-MI. As this dose was not studied in REDUCE-AMI, these findings are complementary and confirm only that high dose BB therapy provides no benefit post-MI in patients with preserved EF. RCTs to assess the benefit of low dose BB therapy post-MI with preserved EF are needed.

Circulation, Volume 150, Issue Suppl_1, Page ASu907-ASu907, November 12, 2024. Background:Abnormal potassium levels are common findings in the intensive care unit (ICU) population. We aimed to determine the incidence of dyskalemias at ICU admission and their association with functional outcome in comatose patients resuscitated from cardiac arrest.Hypothesis:We hypothesized that both hypokalemia and hyperkalemia are associated with unfavorable functional outcome.Methods:Pooled data from four randomized clinical trials in comatose post-cardiac arrest patients admitted to ICU after return of spontaneous circulation (ROSC). Reference potassium levels were defined as between 3 and 4.9 mmol/L, as proposed in the Simplified Acute Physiology Score II. Favorable functional outcome was defined as a Cerebral Performance Category of 1 or 2 at 180 days.Results:We included 1133 patients (557 from HYPERION, 346 from TTH48, 120 from COMACARE and 110 from Xe-HYPOTHECA) with a median age of 64 (IQR: 55-72) years and a predominance of males (72%). Overall, 421 (36%) patients had favorable functional outcome. On admission, 221 (19.5%) patients experienced hyperkalemia and 35 (3.1%) patients experienced hypokalemia. More patients in the normokalemia group (364/877, 41.5%) had a favorable functional outcome, as compared to the hypokalemia (11/35, 31.4%) and hyperkalemia (41/221, 18.6%) groups p